Nivolumab + Chemoradiation in Stage II-IVB Nasopharyngeal Carcinoma (NPC)

PRIMARY OBJECTIVES: I. To establish the feasibility of treatment completion of a combined chemoradiation-nivolumab regimen followed by adjuvant nivolumab. SECONDARY OBJECTIVES: I. To determine the overall response rate at 1 year from end of treatment, as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. II. To determine the locoregional control rate at 1 year post-treatment. III. To determine the distant metastasis rate at 1 year post-treatment. IV. To determine the rate of Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) clearance at end of chemoradiation and at 1 year from end of treatment. V. To determine the acute and late toxicity rates according to Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5, including immune-related adverse events (AEs). VI. To assess patients' quality of life from baseline through 1 year from end of treatment. EXPLORATORY OBJECTIVES: I. To determine the overall survival rate at 5-year post-treatment. II. To determine whether programmed death-ligand 1 (PD-L1) -positive immunohistochemistry and novel quantitative assays correlate to clinical outcome. III. To determine if the density of infiltrating Cluster of differentiation 3 (CD3)+ T cells/μm2 correlates to clinical outcome. IV. To monitor immune changes by flow cytometry in the circulating T cell response to EBV antigens. V. To compare the change in the circulating T-cell repertoire by TCR sequencing and single-cell T-cell profiling. VI. To quantify treatment-induced changes over time in the circulating T cell immune response to EBV using T-cell receptor (TCR) sequencing and enzyme-linked immunospot (ELISPOT) assays. OUTLINE: Patients receive nivolumab intravenously (IV) over 60 minutes on day 1 of courses 1-5 and 7-12. Treatment repeats every 14 days for 11 courses in the absence of disease progression or unacceptable toxicity. Beginning at course 2, patients undergo radiation therapy once daily (QD) 5 days per week and receive cisplatin IV over 30-60 minutes on day 1. Treatment repeats every 7 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 1, 3, 6, 9, and 12 months for up to 1 year and then survival follow-up information may be collected via telephone calls, clinic follow-up visits, or medical records review for up to an additional 4 years. Survival and disease status will be collected until participant death, withdrawal, or if the participant is lost to follow-up.